Now, a new study published on the preprint server medRxiv * aims to analyze the immune response over time, using multi-omics in the study of a single cell. The Study: Multi-Omics Over Time
The researchers from Yale University examined 18 paired samples collected at 2 different time points from all but 2 patients with progressive illness who died before a second sample was available. The samples contained peripheral blood mononuclear cells (PBMCs), obtained from 10 COVID-19 patients with a range of outcomes, in addition to 13 samples from healthy controls who were age-matched.
Among the 10 patients, 4 had progressive disease and expired, with 6 having stable disease culminating in discharge. Tocilizumab was used for 8/10 patients. All patients were similar when the baseline and timeline characteristics were compared.
They employed different approaches, including 5' single-cell RNA sequencing for gene expression (GEX), Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), and B and T cell receptor repertoire analysis. They matched the multi-omics results with clinical and laboratory data, including the viral load and plasma level of various cytokines, taken over a period of time. Type 1 IFN Response
They found that all cell types show a continually changing type-1 interferon (IFN) response, which lessens over time. It tends to increase from the first to the second sample in progressive patients. Both IFN-activated CD8 T cells and ISGs are increased as part of this response. IL-10 and MHC-II Levels
IL-10 expression also follows the same trend, declining in stable patients but increased in progressive patients. MHC-II levels are reduced, and this combination ensures a reduction in inflammation-related organ damage but also reduces the body's ability to clear the viral response. They also found that this correlates with a reduction in viral load and that both are more obvious in COVID-19 patients with progressive disease. AREG Expression
Secondly, they found that monocytes are expressing anti-inflammatory cytokines in progressive COVID-19. This includes expression of amphiregulin (AREG), which binds to epidermal growth factor receptor, and is involved in wound repair as well as a resolution of inflammation. It is higher in viral lung infections, and mice with SARS-CoV infection develop severe lung disease in the presence of AREG. It is also induced by ISG expression in response to type 1 IFN signaling and has been shown to be increased in the PBMCs of COVID-19 patients as well. ISG Expression
And thirdly, they found that IFN-activated CD8 cells expressing IFN-stimulated genes (ISG), are also a characteristic of extreme illness. Effector T cells and naïve T cells are increased and decreased, respectively, in progressive patients compared to stable patients. The former also have higher plasmablast number and dividing T and natural killer cells as well compared to controls. Activated T Cells and Preterminally Exhausted T Cells Related Stories
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